The following discussion of the background of the invention is merely provided to assist the reader in understanding the invention, and is not admitted to describe or constitute prior art to the present invention.
Multimodal imaging probes are highly desirable for in vivo diagnosis due to their ability to be detectable in multiple mode techniques, leading to more accurate and reliable data.1 Multimodal probes that possess magnetic resonance (MR) as well as optical imaging capabilities have attracted considerable attention in recent years.1a,2 Magnetic resonance imaging (MRI) offers imaging of opaque tissues in a noninvasive manner with a high spatial resolution.3 However, its limited sensitivity for imaging at the cellular level hampers its applications for molecular imaging.3 Optical imaging, on the other hand, provides high sensitivity for in vivo imaging, but suffers from low tissue penetration.4 The integration of MRI and optical imaging could act synergistically by improving the resolution and sensitivity.5 In this regard, numerous efforts have been dedicated to the fabrication of bimodal imaging contrast agents, such as Gd-Cy5.5/magnetic nanoparticles (NPs),6 NaYF4/Si-DTTA-Gd3+ NPs,7 Fe2O3/CdSe (ZnS) NPs,8 and Gd2O3/C nanoshells.9 
In particular, lanthanide nanocrystals (NCs) have been actively pursued as multimodal probes due to their unique paramagnetic and luminescent properties. Paramagnetic lanthanides, owing to their unpaired electrons, have been found to be useful as MRI contrast agents, which enhance the visualization of MRI signals. The use of MR contrast agents, which usually constitutes paramagnetic species, can enhance the contrast between normal and malignant tissues by greatly enhancing the water proton's longitudinal (T1) or transverse (T2) relaxation rate, the effect which is widely known as proton relaxation enhancement (PRE).10 T1 contrast agents, which typically include—paramagnetic complexes containing Gd3+ and Mn2+ ions, induce bright MR images in T1-weighted experiments by increasing the spin-lattice relaxation rate of nearby water protons. In contrast thereto, T2 contrast agents, which commonly consist of superparamagnetic NPs (e.g., iron oxide NPs) cause protons in their vicinity to undergo fast spin-spin relaxation which gives rise to dark MR images in T2-weighted experiments.11 A dual-mode imaging strategy, where T1 and T2 MR imaging modes can be utilized simultaneously, has the potential to obtain more comprehensive and complementary diagnostic information. For such purpose, Gd-labeled magnetite NPs12 and “magnetically decoupled” MnFe2O3—Gd2O(CO3)2 core/shell NCs were designed as dual-contrast agents for T1- and T2-weighted MR imaging.13 Ultrasmall superparamagneticiron oxide (USPIO) NPs, capable of depicting enhanced T1 and weak T2 contrast effects at low concentration range, have been developed.14 A FeCo-graphitic system has also exhibited a high T1 and T2 contrast effect, however, an understanding of the mechanism by which this system operates is still unclear.15 
In addition, compared to conventional imaging probes such as organic fluorescent dyes and quantum dots (QDs), lanthanides exhibit multicolor and sharp emission with high quantum yield, long luminescence lifetimes, and low toxicity.16 These excellent features, coupled with their high resistance to photobleaching, make them highly suitable as alternatives to organic dyes and QDs for various biological applications.16 Lanthanides also possess the ability of converting near-infrared (NIR) light (usually 980 nm) to higher energies ranging from UV to the NIR, a process known as up-conversion (UC), which is strongly desirable for biological applications as it gives rise to deeper light penetration, reduced autofluorescence and light scattering, and increasing image contrast.17 A persisting bottleneck in achieving simultaneous UC fluorescence and dual T1, T2 MRI contrast in single lanthanide nanocrystals is the presence of dysprosium (Dy3+) ions, which are up-converter quenchers. Dy3+ ion, despite being a “poison” for UC emission, can enhance the transverse relaxation rate of water protons in tissues.17 They are regarded as promising T2 contrast agents in MRI, as they can provide better spatial resolution and higher contrast to noise ratio at higher magnetic field (>1.5 T).11 
However, there is still a need to provide further contrast agents, in particular dual modal contrast agents.